Impact of Early Parenteral Nutrition Completing Enteral Nutrition in Adult Critically Ill Patients (EPaNIC)
|Critical Illness Starvation||Other: Withholding PN during the first week of ICU stay Drug: Oliclinomel N71000 OR N71000E // Clinimix N17G35 OR N17G35E||Phase 4|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Impact of Early Parenteral Nutrition Completing Enteral Nutrition in Adult Critically Ill Patients|
- Length of stay in ICU and length of stay in the hospital. [ Time Frame: 2 years ]
- Death (hospital and ICU mortality and 90 days mortality) [ Time Frame: 10 years ]
- Days to weaning from mechanical ventilation [ Time Frame: 2 years ]
- The need for renal replacement therapies [ Time Frame: 2 years ]
- The presence or absence of new kidney injury during intensive care [ Time Frame: 2 years ]
- Days of vasopressor or inotropic support [ Time Frame: 2 years ]
- The presence or absence of signs of ICU liver disease: hyperbilirubinemia (defined as bilirubin level > 3 mg/dl), presence of liversteatosis, sludge… [ Time Frame: 2 years ]
- The need for tracheotomy [ Time Frame: 2 years ]
- The presence or absence of hyper-inflammation within five days after ICU admission [ Time Frame: 2 years ]
- Blood lipid profiles and albumin on days one, five, ten, and fifteen after admission [ Time Frame: 2 years ]
- The presence or absence of bacteraemia, ventilator-associated pneumonia and of wound infections [ Time Frame: 2 years ]
- Episodes of hypoglycaemic events (defined as glycemia less than 40 mg/dl) [ Time Frame: 2 years ]
- Amount and type of calories delivered [ Time Frame: 2 years ]
- Muscle strength: among others: MRCss, Maximum Inspiratory Pressure in patients staying more than 7 days in ICU and a subset staying < 7 days, as well as in individuals who have never stayed in ICU. Presence of electrophysiological signs of CIP/CIM. [ Time Frame: 10 years ]
- Rehabilitation/functionality: among others: six minute walking distance and activities of daily life at hospital discharge and at follow-up moments. SF 36 questionnaire at several follow-up moments and in individuals who have never stayed in ICU. [ Time Frame: 10 years ]
|Study Start Date:||August 2007|
|Estimated Study Completion Date:||December 2021|
|Primary Completion Date:||February 2011 (Final data collection date for primary outcome measure)|
|Experimental: EN only||
Other: Withholding PN during the first week of ICU stay
Patients in this arm will receive exclusively enteral nutrition. If enteral nutrition is insufficient after the seventh day of ICU stay, parenteral nutrition will be started.
|Active Comparator: EN plus early PN||
Drug: Oliclinomel N71000 OR N71000E // Clinimix N17G35 OR N17G35E
PN will be started the morning of the third ICU hospitalisation day. The amount of PN to be given will be calculated to cover the caloric needs of the patient, based on the enteral energy intake the previous 24 hours.
Other Name: Parenteral nutrition ATC code B05BA10
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Written informed consent will be obtained from the patient or the closest family member or legal guardian. The family member or the patient can withdraw from the trial, at any time, without impact on his treatment or penalty. The investigators confirm that this study concerns a condition that directly threatens patient health and that the adult patient not able to give consent suffers from the condition. The experiment is essential to confirm the results from earlier research in patients who could consent or from other research methods.
On admission patients will be randomly assigned to receive EN combined with early PN or only EN. At ICU admission, consecutive patients will be randomly assigned to one of these two treatment groups using blinded envelopes, stratified according to primary diagnostic category on admission. Upon addition of the new study site, the numbered en sealed envelopes for randomization stratified according to primary diagnostic category on admission were replaced by an identical digital system allowing central randomization.
As initial nutritional support, patients randomised to the 'EN combined with early PN' group will receive glucose 20% at 40 ml/hr. EN will be initiated in the evening of the second ICU hospitalisation day, PN will be started the morning of the third ICU hospitalisation day. The amount of PN to be given on any particular day will be the difference between calculated caloric needs and the calories delivered by EN the previous 24 hours. When EN covers 80% of calculated caloric needs PN will be stopped. When the patient is able to eat, the parenteral regimen will be reduced and eventually stopped. Whenever oral (+ enteral) intake is below 50% of calculated caloric needs, the PN will be (re)-started.
As initial nutritional support, patients randomised to the 'EN only' group will receive glucose 5% at 40 ml/hr. EN will be initiated on the evening of the second ICU day. From the morning of the third ICU hospitalisation day on, the amount of glucose 5% to be given will be the same as the volume of PN the patient theoretically would require to receive 100% of presumed caloric needs based on the amount of EN delivered the previous 24 hours. When the patient is able to eat, the parenteral regimen (glucose 5%) will be reduced to 50% and eventually stopped. Whenever oral (+ enteral) intake is below 50% of calculated caloric needs, the PN (glucose 5%) will be (re)-started. If these patients would need to stay for more than seven days on the ICU and enteral feeding of at least 80% of the calculated calories is not possible, they will be switched to EN and PN on day eight.
Common strategy for attempting early enteral nutrition in both study arms:
EN will be initiated on the evening of the second ICU day, unless patients are able to eat. The increase of enteral feeding volume and the adaptation of the regimen to pathological conditions will be according to protocol. Trace elements, minerals and vitamins will be administered daily intravenously (IV) to all patients from the day of admission onwards. IV substitution will be stopped in patients receiving at least 1500 ml of EN. All patients will be treated following the intensive insulin therapy schedule - targeting a blood glucose level of 80 - 110 mg/dl - from admission until discharge or oral feeding.
Patients will be weaned from the ventilator according to a standard protocol. End-of-care decisions in patients for whom further intensive care is considered to be futile will be taken in consensus by a group of two senior ICU physicians and the referring specialist, all blinded to study treatment allocation.
In a subgroup of patients, pathways of inflammation and metabolism and the endocrinological impact of the intervention will be studied in blood samples and in snap-frozen in vivo biopsies of muscle and adipose tissue. Blood and tissue samples from healthy volunteers will serve as references for these exploratory studies. In some patients, radiological evolution of regional muscle and adipose tissue volumes will be evaluated.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00512122
|Surgical Intensive Care Unit Regional Hospital Jessa|
|Hasselt, Belgium, 3500|
|Medical Intensive Care Unit|
|Leuven, Belgium, 3000|
|Surgical Intensive Care Unit, Catholic University Leuven University Hospitals|
|Leuven, Belgium, 3000|
|Study Director:||Greet Van den Berghe, MD Ph D||Director of the Department of Intensive Care Medicine Catholic Univeresity Leuven|
|Principal Investigator:||Michaël P Casaer, MD||Department of Intensive Care Medicine Catholic University Leuven|
|Principal Investigator:||Alexander P Wilmer, MD Ph D||Department of Medicine Catholic University Leuven|
|Principal Investigator:||Jasperina Dubois, MD||Surgical Intensive Care Unit Regional Hospital Jessa|